Glycation or non-enzymatic glycosylation involves reaction of amino groups of proteins, lipids, or nucleic acids with sugar aldehyde or keto groups to produce modified amino groups and eventually forming advanced glycosylation end-products (AGE). Glycation may be the first step in a series of slow reactions in the body known as Amadori reactions, Schiff base reactions, and Maillard reactions and lead to advanced glycation endproducts (AGEs). Although glycation is slow in vivo, the glycation products may be reactive, or may have long-lasting effects and the presence of AGE is related to ageing and pathological conditions. In physiological conditions where there is an abundance of sugar molecules available for reaction, such as those where sugar levels are elevated, e.g. diabetes, glycation effects may be more pronounced. Some AGEs are benign, but others are more reactive, and are implicated in many age-related chronic diseases such as, type II diabetes mellitus, cardiovascular diseases, Alzheimer's disease, cancer, peripheral neuropathy, and other sensory losses such as deafness and blindness. Glycation also plays a role in lipid and RNA/DNA modifications.
Glycated substances arc eliminated from the body slowly, since the renal clearance factor is only about 30%. This fact is used to provide a method of testing for sugar levels in diabetics. Red blood cells have a lifespan of 120 days and are easily accessible for measurement of recent increased presence of glycating product. The glycated hemoglobin level, also known as HbA1c, is determined and indicates the level of glycation occurring in the person.
Currently, aminoguanidine is used to slow down glycation by reacting with sugars and blocking the Amadori reactions. Aminoguanidine can reduce both in vitro and in vivo glucose-derived AGE. Aminoguanidine, a nucleophilic hydrazine compound, is currently being studied for use as treatment for AGE complications in diabetes. Additional drugs that inhibit AGE formation or disrupt already formed AGEs (e.g., AGE-breakers) are also under active investigation. For example, a reversal of vascular inelasticity leading to improvement of systolic hypertension and severe heart failure has been reported with AGE-breakers.
Diabetes is a metabolic disorder caused by a deficiency of insulin and is generally diagnosed by an increased blood glucose level. The disorder is characterized by a reduced glucose uptake of the insulin-dependent tissues. The disorder can be controlled by insulin injections but the long-term complications for diabetics include pathologies in the eye (cataractogenesis and retinopathy), kidney (nephropathy), neurons (neuropathy) and blood vessels (angiopathy and atherosclerosis). Glycation plays a role in the pathologies associated with diabetes.
Studies have shown that AGE may have a role in the development of atherosclerosis. Monocytes have AGE specific receptors (RAGE) and respond when stimulated by releasing cytokines. Minor injury to the blood vessel wall may expose sub-endothelial AGE, promote the infiltration of monocytes and initiate the development of atherosclerotic lesions. Circulating lipoproteins can also undergo glycation, which are then taken up by endothelial ceils at a faster rate than non-glycated lipoprotein.
Intake of compositions that can counteract the long-term effects of AGE formation and prevent or treat AGE-related pathologies would be beneficial. Providing such compounds in easily consumed products, such as beverages or sweetener compositions, would be useful in the prevention or treatment of glycation related conditions.